Evidence for Hox-specified positional identities in adult vasculature.
Evidence for Hox-specified positional identities in adult vasculature.
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DOI：
10.1186/1471-213x-8-93
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发表时间：
2008-09-30
影响因子：
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通讯作者：
Awgulewitsch A
中科院分区：
文献类型：
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作者：
Pruett ND;Visconti RP;Jacobs DF;Scholz D;McQuinn T;Sundberg JP;Awgulewitsch A
在成人心血管系统中指定位置信息的概念在很大程度上是未被探索的。虽然HOX转录调控因子必须被视为承担这一角色的优秀候选者，但人们对其可能的心血管控制功能和体内表达模式知之甚少。我们证明了转基因小鼠中传统的报告基因分析是确定成人血管网络中高度复杂的HOX表达模式的有用方法，例如我们的Hoxa3和Hoxc11的LacZ报告基因模型。这些小鼠在血管平滑肌细胞(VSMCs)和内皮细胞(ECs)的亚群中表达，这些细胞位于血管系统的不同区域，大致对应于这两个基因的胚胎表达区域。通过免疫标记和聚合酶链式反应分析，证实这些报告基因模式是内源基因表达的可靠指标。此外，我们还表明，来自血管外植体的培养细胞中持续的报告基因表达有助于体外表型特性的表征，例如Hoxc11-LacZ阳性细胞与阴性细胞在迁移试验和血清中的不同反应。这些数据支持成人血管中HOX特定位置同一性的概念模型，这对于理解心血管系统区域生理差异的机制可能具有相关性。这些数据还表明，传统的HOX报告基因小鼠是可视化血管网络中复杂的HOX表达模式的有用工具，否则可能无法获得这些模式。最后，这些小鼠是分离具有不同HOX表达谱的特定血管细胞亚群并进行表型鉴定的资源。
The concept of specifying positional information in the adult cardiovascular system is largely unexplored. While the Hox transcriptional regulators have to be viewed as excellent candidates for assuming such a role, little is known about their presumptive cardiovascular control functions and in vivo expression patterns. We demonstrate that conventional reporter gene analysis in transgenic mice is a useful approach for defining highly complex Hox expression patterns in the adult vascular network as exemplified by our lacZ reporter gene models for Hoxa3 and Hoxc11. These mice revealed expression in subsets of vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) located in distinct regions of the vasculature that roughly correspond to the embryonic expression domains of the two genes. These reporter gene patterns were validated as authentic indicators of endogenous gene expression by immunolabeling and PCR analysis. Furthermore, we show that persistent reporter gene expression in cultured cells derived from vessel explants facilitates in vitro characterization of phenotypic properties as exemplified by the differential response of Hoxc11-lacZ-positive versus-negative cells in migration assays and to serum. The data support a conceptual model of Hox-specified positional identities in adult blood vessels, which is of likely relevance for understanding the mechanisms underlying regional physiological diversities in the cardiovascular system. The data also demonstrate that conventional Hox reporter gene mice are useful tools for visualizing complex Hox expression patterns in the vascular network that might be unattainable otherwise. Finally, these mice are a resource for the isolation and phenotypic characterization of specific subpopulations of vascular cells marked by distinct Hox expression profiles.